Preliminary studies in this laboratory have demonstrated the feasibility of utilizing the in vitro electrophysiology of spontaneously active cerebellar Purkinje cells as a bioassay for determining the relative central nervous system (CNS) toxicities of various environmental pollutants. We have already shown that hypoxia and carbon monoxide (CO) have marked effects on the activity of these cells. Because of the prevalence of these toxic substances in the environment and the demonstrated effects of these agents on in vivo cerebellar function, we now want to quantitate and extend these studies of hypoxia and CO, and include methyl mercury poisoning. The functional characteristics of CNS bioelectric activity are due, in part, to the complex and dynamic interrelationships of various synaptic networks such as those found in our cerebellar cultures. Accordingly, we intend to continue the development of this relatively rapid bioassay technique, which specifically addresses this crucial aspect of CNS toxicity. Toward that end, we plan to determine the dose-response functions between each of the toxic substances and the quantitative measures of CNS cellular and synaptic network viability, as monitored electrophysiologically. Because both chronic and acute exposures to these toxic substances are important clinical considerations, we will use both types of insults in this study. The particular characteristics of our in vitro preparation will also allow the direct comparison of similar doses delivered acutely and chronically, a comparison not easily obtained with most in vivo bioassays. Finally, because of the demonstrated capacities of this model system for basic neurophysiological investigations, we intend to go beyond toxicological dose-response determinations, per se, and investigate the cellular mechanisms underlying the toxic actions of these substances.